The objectives of this project are to define the role of the human T lymphotropic virus type I (HTLV-I) and related human retroviruses in chronic-progressive myeloneuropathy termed HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). These studies focus on biological and molecular aspect of these human retroviruses as well as on the cellular immune response of the infected individuals to the identified retrovirus agents. These analyses should provide information regarding the pathogenesis of these retroviruses in neurologic diseases and lead to the development of clinical strategies for treatment. Long-term T-cell lines expressing endogenous human retrovirus have been established from affected individuals. These lines have been used to characterize these viral agents molecularly. The polymerase chain reaction, in particular, is being applied to this problem. Human retroviruses are also being characterized by in situ hybridization of brain and spinal cord tissue of HAM/TSP patients. Cellular immune responses of HAM/TSP patients are being investigated, with particular attention to the role of cytotoxic T cells (CTL) in the pathogenesis of this disease. Circulating CTL have been demonstrated from the peripheral blood of these patients but not from HTLV-I carriers. Moreover, these studies have been extended to the demonstration of CTL in the cerebrospinal fluid of HAM/TSP patients. Collectively, these results support a pathogenic role for HTLV-I-specific CTL in the pathogenesis of HAM/TSP.